We propose to determine the role of superoxide dismutase (SOD) in erythrocyte metabolism. With in vitro studies we demonstrated that this cuprozine enzyme inhibits methemoglobin formation and also prevents membrane lysis under circumstances in which superoxide is generated. The in vivo consequences of superoxide deficiency are now under study. Deficiency is produced by dietary copper deprivation. Abnormalities in hemoglobin and in erythrocyte membrane function will be monitored. The function and mechanism of action of ceruloplasmin will be studied. When administered to copper deficient animals, this plasma copper protein induces release of iron to plasma. With double-isotope ferrokinetic techniques, we propose to determine the cell acted upon by ceruloplasmin. We also are searching for ceruloplasmin receptors on spleen and liver cells. Stable isotope tracer techniques for copper are being developed because current radioisotopes are unsatisfactory. The copper in biologic materials is bound to volatile chelating agents and subjected to gas chromatography followed by mass spectrometry. The method can be used for safe and long-term studies of copper kinetics in experimental animals and patients.